Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this observational study found that insulin use in diabetics was associated with higher rates of end-stage kidney disease.

Be aware that the importance of HbA1c level as a predictor of kidney disease differed substantially among insulin-exposed and non-exposed individuals.

CHICAGO -- The use of insulin in type 2 diabetes patients was tied to an increased risk of end-stage renal disease (ESRD), researchers reported here.

In a study of U.S. veterans currently on insulin, and compared with those who were not, insulin use in individuals with HbA1c levels of ≥8.5 was associated with ESRD (HR 2.10, 95% CI 1.93-2.27), according to Srinivasan Beddhu, MD, of the University of Utah Health Care in Salt Lake City, and colleagues.

Individuals with HbA1c levels from 7-8.5 also had a higher risk (HR 1.91, 95% CI 1.75-2.08), as did patients with HbA1c levels <7 (HR 1.97, 95% VI 1.79-2.16), they reported in a poster presentation at the American Society of Nephrology's Kidney Week meeting.

"Independent of HbA1c levels, use of insulin was associated with increased risk of ESRD in type 2 diabetes," the authors wrote. "Indeed, even in those with HbA1c <7, need for insulin was associated with increased ESRD risk," adding that interventions that decrease the need for insulin might lower the risk of ESRD in these patients.

However, Beddhu warned that the study results should note be seen as demonstrating causation. "We need to be cautious in interpreting observational data," he said.

His group hypothesized the progression of chronic kidney disease may be linked to insulin use, as previous literature has noted an association between systemic insulin use and an increased risk of atherosclerosis.

"Obesity is known to cause pancreatic islet cell failure, which in turn will increase the need for insulin use," added Beddhu in an interview with MedPage Today. "We used insulin use as a surrogate marker of islet cell failure and/or insulin resistance."

The researchers examined a cohort of 188,544 veterans with type 2 diabetes, who were divided into six groups based on insulin use and HbA1c levels. Data on serum creatinine levels and serum HDL-cholesterol were gathered within 3 months of one another. Routine lab work and information on current medication use among the participants was gathered, in addition to ESRD status.

Using Cox regression models, the researchers adjusted for several factors including atherosclerosis, blood pressure, body mass index, estimated glomerular filtration rate (eGFR), use of ACE/ARB inhibitors, use of sulfonylurea, and metformin use.

There were 5,757 ESRD events over 1,463,762 years of follow-up. Among insulin users, the authors reported:

Insulin requirement was found to be an independent risk factor of ESRD alone. "We thought insulin use [would] be associated with higher risk of ESRD," Beddhu told MedPage Today. "However, we were surprised to note that on those on insulin, HbA1C ranges that we looked at were not predictive of ESRD."

The researchers highlighted the relationship between requirement for insulin in type 2 diabetes patients and risk of ESRD may be closely related. They suggested that "interventions that decrease the need for insulin might decrease the risk of ESRD in type 2 diabetes."

A study limitation was the lack of data on duration of diabetes.

Beddhu pointed out that "insulin use might reflect islet cell failure, insulin resistance, failure/contraindication to other hypoglycemic agents, or practice patterns. All of these might increase the risk of ESRD. However, a causal role of insulin on the risk of ESRD cannot be excluded based on these data. Irrespective of the underlying mechanisms, interventions that decrease insulin use might decrease ESRD risk. We hope to pursue those on future [randomized clinical trials]."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

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